The objective of this research project will be to study the interaction between glucocorticoids and somatomedin, specifically as related to GAGS biosynthesis and glucocorticoid receptors in cartilage cells. Both of the hormones are essential for optimal growth, yet, in large doses, glucocorticoids inhibit growth and somatomedin over stimulates growth, especially in cartilage. The interaction of these two hormones in cartilage is not known. We will study the effect of both hormones on the biosynthesis of specific types of protein in cartilage, i.e., collagen, chrondomucoproteins and proteins in general, the effect of these hormones on specific steps in GAGS biosynthesis, and, in addition, the effects of somatomedin on the binding of glucocorticoids to sterospecific cartilage glucocorticoid receptors. Demonstration of a reciprocal action of these two hormones may greatly aid in our understanding of the mechanism of glucocorticoid induced growth retardation, as well as our understanding of the effects of somatomedin stimulation on long bone growth. A further objective of this research will be to follow-up and further define our observations on the glucocorticoid effect on embryonic cardiac tissue. We observed that embryonic chick hearts are greatly enlarged after glucocorticoid administration, while in the same embryo, cartilage growth and GAGS biosynthesis was markedly inhibited. We propose to study the effect of glucocorticoid on cartilage and cardiac tissue as to content, histology, GAGS biosynthesis, development of sterospecific glucocorticoid receptors and induction of specific enzyme systems. These studies may greatly aid our understanding of the mechanism of glucocorticoid induced growth retardation as well as provide further insight as to the interaction of somatomedin with other hormones which facilitate or inhibit cartilage growth.